WEBVTT 00:00:00.000 --> 00:00:03.060 These three things is the autistic phenotype. 00:00:03.240 --> 00:00:07.160 You name me. You go find me one autistic phenotype 00:00:07.160 --> 00:00:10.279 that does not have problems with the central 00:00:10.279 --> 00:00:12.519 nervous system, the peripheral nervous system, 00:00:12.519 --> 00:00:15.080 and the enteric nervous system. You can't. You 00:00:15.080 --> 00:00:19.140 can't find it. There we go. Okay, this one's 00:00:19.140 --> 00:00:21.379 going to be dense. This one's going to be fun. 00:00:22.339 --> 00:00:24.280 This is neural relation. We're going to cover 00:00:24.280 --> 00:00:29.429 specifically two episodes we did on We're just 00:00:29.429 --> 00:00:38.689 writing down here. 56 is called Autism Neuralation 00:00:38.689 --> 00:00:42.210 and Autism Neuralation and Embryogenesis. Episode 00:00:42.210 --> 00:00:46.429 57. Neuralation. Neuroepithelial cells and mesencephalon. 00:00:47.409 --> 00:00:51.329 Which is a type of neuroepithelial cell. Oh, 00:00:51.329 --> 00:00:56.130 I'm close. We'll make it. We're gonna make this. 00:00:56.859 --> 00:00:59.619 Tryptophan. These two kind of will branch off 00:00:59.619 --> 00:01:03.539 out of these two. Nicely. You'll see. Hopefully. 00:01:04.159 --> 00:01:07.019 And they're way back. Way back in the old episode. 00:01:07.140 --> 00:01:12.480 We really went into kind of embryogenesis to 00:01:12.480 --> 00:01:16.939 kind of perinatal. Just after birth. I think. 00:01:17.180 --> 00:01:19.540 Maybe up to two years. I can't remember. I can't 00:01:19.540 --> 00:01:23.859 remember actually. But we spent a lot of time 00:01:23.859 --> 00:01:28.189 UC San Diego. Every tower they spend a lot of 00:01:28.189 --> 00:01:31.250 time on in this little epoch. It's great stuff. 00:01:31.250 --> 00:01:36.290 They have great data That episode really went 00:01:36.290 --> 00:01:40.730 into kind of artificial light we're gonna get 00:01:40.730 --> 00:01:45.829 there though, so We're kind of gonna be talking 00:01:45.829 --> 00:01:49.250 about these two episodes mostly so I just spent 00:01:49.250 --> 00:01:52.969 a lot of time writing those episodes out I probably 00:01:52.969 --> 00:01:57.500 shouldn't have done that just stick to this kind 00:01:57.500 --> 00:02:01.680 of like the objective of the information. So 00:02:01.680 --> 00:02:05.420 we're going to talk about Neuralation and Embryogenesis, 00:02:05.640 --> 00:02:08.919 and this is the Neuroplate, okay? So this comes 00:02:08.919 --> 00:02:14.020 on board around day 21, 23 or so. This is what 00:02:14.020 --> 00:02:18.219 we are to begin with. The glare is okay, I think. 00:02:18.340 --> 00:02:21.439 Neuroplate. So we got the Epidermis in the blue. 00:02:22.920 --> 00:02:25.180 neuroectoderm is here in the middle and then 00:02:25.180 --> 00:02:27.939 the little green is called a border and then 00:02:27.939 --> 00:02:31.599 this thing folds see this this will fold in and 00:02:31.599 --> 00:02:35.099 the neuroectoderm will come down and this is 00:02:35.099 --> 00:02:40.939 um we have different types of derm now ectoderm 00:02:40.939 --> 00:02:45.659 is at the very edges the mesoderm is the next 00:02:45.659 --> 00:02:48.879 layer kind of in and the endoderm is the center 00:02:48.879 --> 00:02:52.710 of this fold And this is where skin and nervous 00:02:52.710 --> 00:02:56.669 systems will begin. Skin and nervous systems 00:02:56.669 --> 00:03:02.490 are like that. And then we have the tube, because 00:03:02.490 --> 00:03:05.490 we're folding into a tube. And we have the epidermis. 00:03:05.949 --> 00:03:09.409 It's growing larger, okay. It started here. We 00:03:09.409 --> 00:03:12.949 have the epidermis on top. And then the green 00:03:12.949 --> 00:03:17.289 are neurocrest cells. And then we have the tube, 00:03:17.729 --> 00:03:21.099 which is right here, the neuroectoderm. So when 00:03:21.099 --> 00:03:25.379 Jack Crew says things like the skin and the oral, 00:03:25.860 --> 00:03:28.379 oral tissues and so forth, and the central nervous 00:03:28.379 --> 00:03:31.840 system are combined. They're like that. So this 00:03:31.840 --> 00:03:35.439 tube will go on to develop the brain and spine, 00:03:35.719 --> 00:03:38.400 the central nervous system. These neurocrest 00:03:38.400 --> 00:03:41.439 cells, they're just kind of drawn as circles. 00:03:42.620 --> 00:03:47.520 This is where already on board melanocytes, melanocytes 00:03:47.520 --> 00:03:51.159 are being created. Remember because of the skin 00:03:51.159 --> 00:03:56.479 and then the adrenals our adrenals we think of 00:03:56.479 --> 00:04:00.919 things like adrenaline and cortisol and so forth 00:04:00.919 --> 00:04:04.080 and then face and bone and cartridge and then 00:04:04.080 --> 00:04:06.900 here the peripheral and enteric nervous systems 00:04:06.900 --> 00:04:09.340 are beginning so this is more central nervous 00:04:09.340 --> 00:04:13.400 system and this is more peripheral and enteric 00:04:13.400 --> 00:04:18.819 nervous system okay now there's some key components 00:04:18.819 --> 00:04:22.399 here that are very um worth mentioning and we've 00:04:22.399 --> 00:04:27.540 done we've covered these um so just kind of recapping 00:04:27.540 --> 00:04:34.699 these shh what is this we have this and it's 00:04:34.699 --> 00:04:37.980 huge in development sonic hedgehog sonic hedgehog 00:04:37.980 --> 00:04:42.639 this is involved in proliferation So we're going 00:04:42.639 --> 00:04:45.079 to be making cells here, right? We make a lot 00:04:45.079 --> 00:04:48.319 of cells here. We proliferate cells. Cells divide. 00:04:48.879 --> 00:04:53.300 It's kind of just the process. Progenitor cells 00:04:53.300 --> 00:04:58.439 is big with the sonic hedgehog. Progenitor cells 00:04:58.439 --> 00:05:02.279 and cell growth. And they control, sonic hedgehog 00:05:02.279 --> 00:05:06.379 will also control cell survival. Sonic hedgehog 00:05:06.379 --> 00:05:12.000 is involved with motor neurons and Interneurons. 00:05:12.839 --> 00:05:16.579 What are those? We could simplify neurons in 00:05:16.579 --> 00:05:19.899 the central nervous system as sensory neurons, 00:05:20.639 --> 00:05:23.779 interneurons, and motor neurons. If we want to 00:05:23.779 --> 00:05:26.639 really have like a simplistic view of things. 00:05:27.100 --> 00:05:29.819 Sensory neurons, they're involved with sensory 00:05:29.819 --> 00:05:33.220 input. Interneurons are things that are connecting 00:05:33.220 --> 00:05:37.019 regions. Things like excitation inhibition. And 00:05:37.019 --> 00:05:39.610 then the motor neurons are responsible for Things 00:05:39.610 --> 00:05:42.050 I'm doing right now. Just moving. I'm constantly 00:05:42.050 --> 00:05:47.649 moving. EI is a big one here. From here. Okay. 00:05:48.069 --> 00:05:52.230 Now, if you look at data, research data, and 00:05:52.230 --> 00:05:56.029 you can find like mice and rat models of autism. 00:05:57.389 --> 00:06:01.910 If you knock out, it will look like this. Sonic 00:06:01.910 --> 00:06:06.490 Hedgehog knock out. The mouse or rat will not 00:06:06.490 --> 00:06:11.060 develop the thalymic reticular nucleus. This 00:06:11.060 --> 00:06:17.639 part comes from the ventral thalamus. Okay, so 00:06:17.639 --> 00:06:21.220 if you knock out this in a mouse or rat model, 00:06:21.540 --> 00:06:28.660 they will not develop this or that. So this must 00:06:28.660 --> 00:06:32.740 be a region of interest for us because of this. 00:06:33.579 --> 00:06:36.660 Remember the par of albium interneuron specifically. 00:06:37.240 --> 00:06:41.399 And then this. We've covered that in an episode 00:06:41.399 --> 00:06:44.779 about inhibition. Because that's a sensory gate. 00:06:45.279 --> 00:06:47.660 It protects the thalamus. You don't want the 00:06:47.660 --> 00:06:52.899 thalamus to be over your hand. Insane. Okay, 00:06:53.100 --> 00:06:56.439 okay. We're getting there. Shoot, we're already 00:06:56.439 --> 00:07:00.680 nine minutes in. God bless it. Next one is P10. 00:07:01.680 --> 00:07:06.399 Phosphor... Phos... Four... Case. No, that's 00:07:06.399 --> 00:07:10.660 not right. Phosphortensin. For sure it's tensin, 00:07:10.759 --> 00:07:12.779 but I don't know how to spell it. Let me check 00:07:12.779 --> 00:07:16.699 my notes. That's it? Insane. ACE. Anytime you 00:07:16.699 --> 00:07:20.899 see ACE, it's an enzyme. So this is an enzyme. 00:07:22.459 --> 00:07:25.279 P10. It's huge. This is going to be huge. This 00:07:25.279 --> 00:07:29.019 is a lipid and protein phosphor. I can't spell 00:07:29.019 --> 00:07:34.199 that. I can't. Lipid and protein phosphors. All 00:07:34.199 --> 00:07:37.149 of our membranes except for the inner mitochondrial 00:07:37.149 --> 00:07:40.370 membrane, or lipid. Lipid phosphorus. Every cell 00:07:40.370 --> 00:07:43.490 membrane. This is huge. This is also involved 00:07:43.490 --> 00:07:47.490 with regulating neurolation here. In a large 00:07:47.490 --> 00:07:52.230 part. Okay. There's a pathway P, let me see. 00:07:53.230 --> 00:07:57.769 Yeah. There's a lot of PIP. You'll see a lot 00:07:57.769 --> 00:08:00.689 of PIP involved, like two, three, and so forth, 00:08:01.069 --> 00:08:04.250 with this. But let's not get distracted here. 00:08:05.460 --> 00:08:11.199 AKT and mTOR mammalian target of rapamycin okay 00:08:11.199 --> 00:08:17.160 this is huge in this this process okay especially 00:08:17.160 --> 00:08:21.360 the neural plate okay this is going to be such 00:08:21.360 --> 00:08:24.100 a region of interest this is also involved with 00:08:24.100 --> 00:08:27.139 and because it's lipid and phosphorus microtubules 00:08:27.139 --> 00:08:31.120 we have an episode on that I wrote it out and 00:08:31.120 --> 00:08:37.059 mitochondrial biogenesis okay this there's a 00:08:37.059 --> 00:08:46.240 study recently eric et al in 2021 or 2022 i can't 00:08:46.240 --> 00:08:51.000 remember i can't remember but it's in cell press 00:08:51.000 --> 00:08:56.740 cell press is a fantastic journal uh it's actually 00:08:56.740 --> 00:09:01.100 movie cell reports i can see the graphical abstraction 00:09:01.100 --> 00:09:04.350 so so press Journals have this great graphical 00:09:04.350 --> 00:09:07.610 abstraction and then like three or four key highlights. 00:09:08.169 --> 00:09:13.070 They're it's very good stuff. Okay, so They study 00:09:13.070 --> 00:09:19.289 that a loss of p10 and then mtor Complex one. 00:09:19.730 --> 00:09:24.750 You'll see it as m -t -o -r -c -1 I forget what 00:09:24.750 --> 00:09:27.490 they did. I forget if they rescued the lack of 00:09:27.490 --> 00:09:31.663 p10 by targeting complex one or what I don't 00:09:31.720 --> 00:09:35.600 I don't know. But this is a good region of interest 00:09:35.600 --> 00:09:39.820 here for us. This regulates cell growth, proliferation, 00:09:40.080 --> 00:09:43.000 survival, and differentiation as well. And the 00:09:43.000 --> 00:09:47.000 proliferation here into differentiation into 00:09:47.000 --> 00:09:50.679 a mature cell. P10 is also involved in things 00:09:50.679 --> 00:09:53.620 like cancer growth and things like that. Okay. 00:09:54.139 --> 00:09:56.879 Now we're getting somewhere I think. Because 00:09:56.879 --> 00:09:59.559 we got to get to the mesencephalon. We got to 00:09:59.559 --> 00:10:02.590 get to the mesencephalon big time. And also, 00:10:02.769 --> 00:10:06.429 and we won't spend much time on this one. B9, 00:10:06.429 --> 00:10:12.629 okay. Methylene tetrahydrofolate reductase. No, 00:10:12.690 --> 00:10:18.190 what did I say? Methylene tetrahydrofolate reductase. 00:10:18.509 --> 00:10:21.909 Methylene. This is the motherfucker gene. And 00:10:21.909 --> 00:10:26.090 this is B9. This is leukovorin. Okay, I'm not 00:10:26.090 --> 00:10:28.210 going to sit here and explain this because you 00:10:28.210 --> 00:10:32.480 can go see Richard Fry and Nicole Rincon. Probably 00:10:32.480 --> 00:10:34.879 the best in the world best in the world former 00:10:34.879 --> 00:10:37.759 guest on the podcast best in the world on this 00:10:37.759 --> 00:10:42.840 this phalamic acid and Leukovorin, okay, this 00:10:42.840 --> 00:10:47.039 is building block though for Protein synthesis 00:10:47.039 --> 00:10:50.399 and so forth and DNA methylation. This is a big 00:10:50.399 --> 00:10:53.779 thing that the DNA methylation remember Richard 00:10:53.779 --> 00:10:59.279 Frye we talked about how Leukovorin is helping 00:11:00.179 --> 00:11:03.879 Possibly the distal connections like from the 00:11:03.879 --> 00:11:06.039 superior colliculus to the frontal eye fields 00:11:06.039 --> 00:11:11.240 is a very distal connection or the superior temporal 00:11:11.240 --> 00:11:15.259 gyrus, sometimes verneckis and so forth, to Broca 00:11:15.259 --> 00:11:18.779 for the speech and language. This is going to 00:11:18.779 --> 00:11:22.860 be a big thing here. It's also involved with 00:11:22.860 --> 00:11:28.379 methionine. It provides SAM, the donor or cofactor. 00:11:28.620 --> 00:11:32.399 to methionine methionine and tryptophan which 00:11:32.399 --> 00:11:34.919 we're going to talk about now they are fantastic 00:11:34.919 --> 00:11:37.779 amino acids because they only have one codon 00:11:37.779 --> 00:11:41.759 tryptophan and methionine are so special you 00:11:41.759 --> 00:11:45.580 know this this is an aromatic amino acid this 00:11:45.580 --> 00:11:50.639 means it needs uv light aromatics are uv light 00:11:50.639 --> 00:11:53.519 antennas essentially they have benzene rings 00:11:53.519 --> 00:11:57.980 and um pi electrons and things and so forth which 00:11:57.980 --> 00:12:01.500 helps it synthesize. Tryptophan is like around 00:12:01.500 --> 00:12:09.240 277, 283 type of peak absorption, which is right 00:12:09.240 --> 00:12:13.379 on the line of UVB, UVB sourced at 280. But this 00:12:13.379 --> 00:12:17.799 is huge because maternal peripheral tryptophan 00:12:17.799 --> 00:12:21.320 equals brain. Tryptophan serotonin. The mother 00:12:21.549 --> 00:12:25.389 peripheral tryptophan is how the fetal forebrain 00:12:25.389 --> 00:12:28.029 gets tryptophan and serotonin nobody does anything 00:12:28.029 --> 00:12:30.169 with this stuff though i'm telling you nobody 00:12:30.169 --> 00:12:32.970 nobody cares nobody does anything with this stuff 00:12:32.970 --> 00:12:37.509 this is involved with those sensory maps serotonin 00:12:37.509 --> 00:12:41.409 has massive roles outside of mood outside of 00:12:41.409 --> 00:12:47.440 it's so unbelievable to me serotonin has hidden 00:12:47.440 --> 00:12:50.279 rows, okay, with receptors and cell differentiation 00:12:50.279 --> 00:12:54.840 and proliferation with initially overgrowth of 00:12:54.840 --> 00:12:58.519 neurorites. Neurorites are axons and dendrites. 00:12:59.019 --> 00:13:01.779 How much information do we need about autistic 00:13:01.779 --> 00:13:05.080 phenotype having abnormal axon and dendrite? 00:13:06.080 --> 00:13:10.600 I don't know. I don't know. Especially in the 00:13:10.600 --> 00:13:13.799 central nervous system and the peripheral nervous 00:13:13.799 --> 00:13:17.350 system. Serotonin. Serotonin. It's unbelievable 00:13:17.350 --> 00:13:20.769 to me. The mother's tryptophan levels, remember, 00:13:21.750 --> 00:13:26.509 remember, tryptophan being that aromatic amino 00:13:26.509 --> 00:13:31.730 acid, if it's under hypoxia, okay, so you have 00:13:31.730 --> 00:13:35.350 tryptophan and that synthesizes serotonin and 00:13:35.350 --> 00:13:39.429 then some melatonin, ugh, that's melatonin, okay? 00:13:39.649 --> 00:13:44.340 Oxygen levels will move this this way. Depending 00:13:44.340 --> 00:13:47.100 on your oxygen levels and ROS things like that. 00:13:47.120 --> 00:13:51.860 So it depends on the oxygen and So forth will 00:13:51.860 --> 00:13:54.500 depend on how the tryptophan is being synthesized 00:13:54.500 --> 00:13:57.700 or not being synthesized Nobody cares. I don't 00:13:57.700 --> 00:14:00.240 think I don't know. I don't know what's I don't 00:14:00.240 --> 00:14:03.740 I don't know. I don't know what's Why things 00:14:03.740 --> 00:14:08.240 like this is this? so foreign in autism research 00:14:08.240 --> 00:14:13.000 Okay, anyways, so once we get here once we get 00:14:13.000 --> 00:14:15.960 this we're going to spend more most time here 00:14:15.960 --> 00:14:19.720 for the central nervous system so there's four 00:14:19.720 --> 00:14:23.120 four cell types that will come on board neuro 00:14:23.120 --> 00:14:30.740 epithelial cells which will become four cells 00:14:30.740 --> 00:14:36.639 as well and then let's see the the neural crest 00:14:36.639 --> 00:14:41.169 cells will begin to do different things um the 00:14:41.169 --> 00:14:46.769 ectoderm okay so kind of it's just expanding 00:14:46.769 --> 00:14:49.990 out here and then mesoderm okay it's just you 00:14:49.990 --> 00:14:53.610 know we're we're this and then well maybe like 00:14:53.610 --> 00:14:57.429 that and then we fold and then this another layer 00:14:57.429 --> 00:15:00.110 comes on and then we're just eventually becoming 00:15:00.110 --> 00:15:02.909 you know we're just expanding it's almost like 00:15:02.909 --> 00:15:05.769 a finger looks better because we're about to 00:15:05.769 --> 00:15:08.639 draw this out right now We're about to draw it 00:15:08.639 --> 00:15:11.659 out. We're just gonna get rid of this. Because 00:15:11.659 --> 00:15:15.000 we gotta get to the mesencephalon. We gotta get 00:15:15.000 --> 00:15:18.440 to the mesencephalon. And these epicy of cells. 00:15:19.559 --> 00:15:23.700 So we're just gonna go here, okay? Because we're 00:15:23.700 --> 00:15:26.500 developing the brain here. Brain and spine, central 00:15:26.500 --> 00:15:30.960 nervous system, okay? So I need different colors 00:15:30.960 --> 00:15:34.019 here, I think. I think that's what we'll do. 00:15:35.260 --> 00:15:37.980 Red's gonna be mesencephalon, I think. We'll 00:15:37.980 --> 00:15:41.200 have to do red for mesencephalon. Okay, so we 00:15:41.200 --> 00:15:45.059 have the pro -encephalon. Remember, there's four 00:15:45.059 --> 00:15:54.600 different cell types. Pro -encephalon, mes -encephalon, 00:15:54.820 --> 00:15:59.080 and then we'll go green. We'll go green for the 00:15:59.080 --> 00:16:00.980 rom -encephalon because it's a lot of going, 00:16:01.500 --> 00:16:03.580 a lot of reflexes. And then the fourth one, to 00:16:03.580 --> 00:16:07.740 be honest. It's, it's making the spine. It's 00:16:07.740 --> 00:16:11.539 making the spine. So right after, right after 00:16:11.539 --> 00:16:16.620 that fold and tube and the epidermis coming on 00:16:16.620 --> 00:16:19.620 board, we kind of start looking like this. Okay. 00:16:19.659 --> 00:16:21.299 This is what we're kind of just looking like 00:16:21.299 --> 00:16:26.179 here. Okay. This is pro here, mesencephalon here, 00:16:26.519 --> 00:16:30.480 romencephalon here, spine. All right. So these 00:16:30.480 --> 00:16:33.320 will begin to subdivide. So the proencephalon, 00:16:34.759 --> 00:16:38.200 The forebrain goes into, I hope you guys can 00:16:38.200 --> 00:16:45.500 see this, telencephalon and diencephalon. Okay, 00:16:45.500 --> 00:16:51.259 so essentially this one is the cortex, this one's 00:16:51.259 --> 00:16:54.659 the subcortical areas, okay? And then we'll start 00:16:54.659 --> 00:16:57.000 to look like this. It's almost like a heart. 00:16:59.039 --> 00:17:03.700 Maybe I'll draw it keeping with this theme, okay? 00:17:03.980 --> 00:17:08.619 So we'll start going like this. Okay, it's getting 00:17:08.619 --> 00:17:12.500 bigger, is what we're doing. This one, if you 00:17:12.500 --> 00:17:14.660 know, if you follow along with the podcast and 00:17:14.660 --> 00:17:17.980 me ranting about this all the time, nothing. 00:17:18.180 --> 00:17:23.680 This one will make the MET encephalon and the 00:17:23.680 --> 00:17:27.920 MY encephalon. So this will become the cerebellum 00:17:27.920 --> 00:17:31.220 and pons. And this one is the medulla. Okay, 00:17:31.359 --> 00:17:35.609 so... Let's see, we'll start looking like this. 00:17:35.609 --> 00:17:39.289 Okay, that's good. That's good there. So this 00:17:39.289 --> 00:17:42.809 is the pronencephalon. Okay, it's just The big 00:17:42.809 --> 00:17:45.829 the big head that's it's the majority of our 00:17:45.829 --> 00:17:48.990 brain is right here This is the smallest part 00:17:48.990 --> 00:17:51.130 and then this is the bottom of the brain stem 00:17:51.130 --> 00:17:53.650 or most of the brain stem and then the spine 00:17:53.650 --> 00:18:00.950 Okay, so let's draw this out as the brain All 00:18:00.950 --> 00:18:06.569 right so the proencephalon so It might be easier 00:18:06.569 --> 00:18:09.009 to go bottom up. I'm just going to go bottom 00:18:09.009 --> 00:18:13.769 up So we have the brain stem here the start of 00:18:13.769 --> 00:18:18.009 the brain stem the medulla Okay, this is the 00:18:18.009 --> 00:18:22.130 medulla and then let's see so this this is the 00:18:22.130 --> 00:18:25.269 myencephalon Okay, and then the metencephalon 00:18:25.269 --> 00:18:28.690 the pons is a little football oval shape that 00:18:28.690 --> 00:18:32.039 sticks out in the front side of the the brain 00:18:32.039 --> 00:18:37.059 stem. And then we also have deep inside here. 00:18:37.160 --> 00:18:40.660 It's kind of covered. Sometimes you'll see it 00:18:40.660 --> 00:18:43.619 covered with things like the occipital, temporal. 00:18:44.480 --> 00:18:49.940 Sometimes you won't. It just depends. But I'm 00:18:49.940 --> 00:18:53.519 just going to cover it. And then the mesencephalon. 00:18:53.859 --> 00:18:57.779 Okay. I got to go up higher because the mesencephalon 00:18:57.779 --> 00:19:01.299 is not very big. The mesencephalon will be like 00:19:01.299 --> 00:19:04.880 that. And then I need blue. I need blue here. 00:19:05.299 --> 00:19:08.299 Okay. I gotta finish this out. We might just 00:19:08.299 --> 00:19:10.960 cover it though. So we have that like the occipital 00:19:10.960 --> 00:19:17.339 lobe and the parietal lobe. That sensory motor 00:19:17.339 --> 00:19:22.819 area. The frontal eye fields will be here. And 00:19:22.819 --> 00:19:26.440 then we'll get into the prefrontal cortex. Then 00:19:26.440 --> 00:19:28.420 this kind of, you know, it just kind of comes 00:19:28.420 --> 00:19:32.640 in. and then the temporal lobe kind of do this 00:19:32.640 --> 00:19:38.400 thing right here okay then like your eyes will 00:19:38.400 --> 00:19:42.619 be here retina your eye things like that so this 00:19:42.619 --> 00:19:45.960 is responsible for all of this this is only responsible 00:19:45.960 --> 00:19:50.599 for here and then this is key areas a lot of 00:19:50.599 --> 00:19:54.779 autonomic functioning right here all right so 00:19:54.779 --> 00:19:59.190 let's talk about The big thing here. Oh, this 00:19:59.190 --> 00:20:01.970 is way too long. I gotta clean this stuff up. 00:20:02.230 --> 00:20:04.930 Let's just go ahead and draw this out. Because 00:20:04.930 --> 00:20:09.289 this is the whole part. Everything about autism 00:20:09.289 --> 00:20:14.210 might be able to be explained right here. Everything. 00:20:15.289 --> 00:20:18.930 During this timeline, too. Okay? We talked about 00:20:18.930 --> 00:20:21.750 how the central nervous system, the peripheral 00:20:21.750 --> 00:20:24.589 nervous system, things like the oral microbiome, 00:20:24.799 --> 00:20:26.740 The first time Richard Fry was on the episode, 00:20:26.819 --> 00:20:30.539 he mentioned like a size of a one of the teeth. 00:20:32.160 --> 00:20:37.380 Oh, goodness. My teeth, my teeth thing. I don't. 00:20:37.599 --> 00:20:41.160 I'm not good with molars. One of the molars, 00:20:41.279 --> 00:20:44.420 the size of a molar will predict autism. Richard 00:20:44.420 --> 00:20:49.279 Fry told us that. And AJ Drexel was on that study. 00:20:49.759 --> 00:20:51.779 Kristen Lyaw was on that study. And at what? 00:20:51.799 --> 00:20:54.180 That's what connected me to Kristen Liao, who 00:20:54.180 --> 00:20:57.160 was on in December. Kristen Liao, Modifiable 00:20:57.160 --> 00:20:59.640 Risk Factors with Autism, received one of the 00:20:59.640 --> 00:21:03.160 new NIH grants for investigating autism. Okay, 00:21:03.500 --> 00:21:05.859 let's get into this. I'm going to draw what you 00:21:05.859 --> 00:21:10.880 might think is a butterfly. Okay. I'm going to 00:21:10.880 --> 00:21:13.420 try to do this good, too, because this is going 00:21:13.420 --> 00:21:16.140 to be hard. No, that's not so bad. We're looking 00:21:16.140 --> 00:21:20.450 straight on, straight down. Into the mesencephalon 00:21:20.450 --> 00:21:23.710 here. Okay, so we removed the whole top part 00:21:23.710 --> 00:21:25.589 of the head and we're just looking straight down 00:21:25.589 --> 00:21:29.230 into it Alright, so we're gonna have different 00:21:29.230 --> 00:21:31.730 regions here. Okay, I should have used different 00:21:31.730 --> 00:21:36.170 colors That's fine. This dark spot here is the 00:21:36.170 --> 00:21:42.250 substantia nigra substantia nigra which translates 00:21:42.250 --> 00:21:46.869 into black substance or a substantially black 00:21:47.099 --> 00:21:52.779 black substance okay this is um the mesencephalon 00:21:52.779 --> 00:21:55.259 can be divided into three main parts okay this 00:21:55.259 --> 00:22:01.880 is like a um pre yeah not pre it's like uh i 00:22:01.880 --> 00:22:04.700 don't know cerebral something i have no idea 00:22:04.700 --> 00:22:08.700 what this area is to be honest and it's right 00:22:08.700 --> 00:22:14.480 here the front part okay and then we have might 00:22:14.480 --> 00:22:17.279 as well make it red red nucleus It's involved 00:22:17.279 --> 00:22:19.859 with motor movements, different types of motor 00:22:19.859 --> 00:22:26.180 movements. Okay, we'll go blue for a lot more 00:22:26.180 --> 00:22:30.119 of this stuff. Here, medial geniculate nucleus. 00:22:31.220 --> 00:22:34.779 Okay, this is actually part of the thalamus. 00:22:35.059 --> 00:22:40.000 This is where auditory goes as a relay station 00:22:40.000 --> 00:22:44.160 for the thalamus. because this brain stem coming 00:22:44.160 --> 00:22:46.599 up the brain stem is going to be heavily involved 00:22:46.599 --> 00:22:50.740 with um um auditory sensory and we're going to 00:22:50.740 --> 00:22:53.480 get to the sensory part okay i'm just kind of 00:22:53.480 --> 00:22:57.779 just drawing this stuff out now i want want brown 00:22:57.779 --> 00:23:01.880 for para -aqueductal gray okay let's see this 00:23:01.880 --> 00:23:04.400 part is going to be huge because we talked about 00:23:04.400 --> 00:23:08.900 this part quite in detail superior colliculus 00:23:08.900 --> 00:23:11.660 eye movements eye movements will go right here 00:23:12.559 --> 00:23:16.740 Once it hits the lateral geniculate these will 00:23:16.740 --> 00:23:20.599 send some fibers down to here and this will go 00:23:20.599 --> 00:23:23.059 back up and recruit the frontal eye fields here 00:23:23.059 --> 00:23:25.400 and then just be like a distal connection and 00:23:25.400 --> 00:23:28.279 it helps with modulating our eye gaze and eye 00:23:28.279 --> 00:23:33.940 contact and things like that. So this is also 00:23:33.940 --> 00:23:36.900 receiving inputs just like visual cortex one. 00:23:37.019 --> 00:23:39.859 So I think it's probably like identical timing 00:23:39.859 --> 00:23:46.410 after the lateral geniculate. Okay, so then there's 00:23:46.410 --> 00:23:52.309 also some cranial nerves. Okay, there's some 00:23:52.309 --> 00:23:57.809 cranial nerves. This, this is ocular motor, more, 00:23:59.009 --> 00:24:06.049 more eye movements. Look over here. A thing called 00:24:06.049 --> 00:24:10.410 Edinger Westfall. This is This is kind of some 00:24:10.410 --> 00:24:13.190 eye movements too, but there's some, there's 00:24:13.190 --> 00:24:16.869 some choline involved here. This is, this has 00:24:16.869 --> 00:24:21.009 like two parts to it. Okay. One is the choline 00:24:21.009 --> 00:24:25.150 and it will send information down to ganglia 00:24:25.150 --> 00:24:30.130 ganglion fibers, but this has indirect, um, influence 00:24:30.130 --> 00:24:35.150 with, um, we're almost trying to say pupil constriction 00:24:35.150 --> 00:24:37.960 because I was thinking about the light reflex, 00:24:38.200 --> 00:24:40.960 pupillary light reflex, which is a hidden danger. 00:24:41.220 --> 00:24:44.359 It's a very hidden danger with LEDs and blue 00:24:44.359 --> 00:24:47.839 light. I think this is going to be hitting hard 00:24:47.839 --> 00:24:51.599 because if you think about it too, it's sending 00:24:51.599 --> 00:24:55.640 ganglionic fibers down the spine which is full 00:24:55.640 --> 00:25:01.079 of ganglionic fibers and our eyes with the constriction 00:25:01.079 --> 00:25:04.000 and dilation and so forth with these light flicker 00:25:04.000 --> 00:25:07.799 that we cannot see but it's happening. okay and 00:25:07.799 --> 00:25:11.240 then ocular motor so there's massive amounts 00:25:11.240 --> 00:25:17.859 of um eyes going on here and there's some cranial 00:25:17.859 --> 00:25:21.839 nerves three cranial nerves three and four are 00:25:21.839 --> 00:25:26.720 here um that hole right there i think this is 00:25:26.720 --> 00:25:30.740 where cerebral spinal fluid comes up from the 00:25:30.740 --> 00:25:33.660 spine and then into the brain because right on 00:25:33.660 --> 00:25:41.369 top of the The mesencephalon is this thing. That's 00:25:41.369 --> 00:25:45.950 awful. It looks like a talon. And this area right 00:25:45.950 --> 00:25:48.849 here is full of water. There's not a lot of blood 00:25:48.849 --> 00:25:52.410 -brain barrier here. Looks like a talon. And 00:25:52.410 --> 00:25:58.130 all of these surfaces are surrounding this. When 00:25:58.130 --> 00:26:03.470 you see things like this in the middle of the 00:26:03.470 --> 00:26:08.029 brain, Like the cadet nucleus has a long shell. 00:26:08.809 --> 00:26:11.589 It's like right here. You can see these things. 00:26:11.630 --> 00:26:14.549 There's like a fornax that's extending off from 00:26:14.549 --> 00:26:17.910 the amygdala. It just depends on how lateral 00:26:17.910 --> 00:26:23.970 you are. But you can see it like this. It's a 00:26:23.970 --> 00:26:29.910 paraventricular area right here. Lots of water. 00:26:30.240 --> 00:26:34.279 Lots of water. So this is huge because the mesencephalon 00:26:34.279 --> 00:26:37.259 here I'm just gonna get rid of this stuff because 00:26:37.259 --> 00:26:40.779 the mesencephalon has three main roles Motor 00:26:40.779 --> 00:26:44.099 movement which is the red nucleus, but mainly 00:26:44.099 --> 00:26:47.319 here because this is broken down into two parts 00:26:47.319 --> 00:26:52.099 pars Compacta which is both dopamine. This is 00:26:52.099 --> 00:26:57.880 huge. This is The basal ganglia okay and Parkinson's 00:26:57.880 --> 00:26:59.400 because we're going to I'm going to draw something 00:26:59.400 --> 00:27:02.119 out about Parkinson's real fast here in here 00:27:02.119 --> 00:27:05.660 in a second um and then the other part of the 00:27:05.660 --> 00:27:10.460 substantia nigra is pars reticulata that reminds 00:27:10.460 --> 00:27:13.980 me too the reticular formation is very much involved 00:27:13.980 --> 00:27:17.759 here the reticular formation is if we just draw 00:27:17.759 --> 00:27:21.480 the brain stem again at the start of the cerebellum 00:27:21.480 --> 00:27:26.029 and then you know the mesencephalon is here What 00:27:26.029 --> 00:27:27.670 was I talking about? I forget what I was talking 00:27:27.670 --> 00:27:33.150 about. But the pars reticulata is GABA, okay? 00:27:33.190 --> 00:27:37.210 And this is synonymous with Vomus Pallidus internal. 00:27:38.069 --> 00:27:41.890 The reticulata and Vomus Pallidus internal are 00:27:41.890 --> 00:27:44.529 kind of like output areas of the basal ganglia, 00:27:44.869 --> 00:27:48.009 which is regulating movement, correct and indirect 00:27:48.009 --> 00:27:52.109 pathway. We'll do whiteboard episodes on that 00:27:52.109 --> 00:27:54.960 because it's... heavily involved in parkinson's 00:27:54.960 --> 00:27:58.259 man so bad what was i doing here i don't remember 00:27:58.259 --> 00:28:04.619 but if you can oh never mind sensory integration 00:28:04.619 --> 00:28:08.759 okay multiple forms of sensory you have you have 00:28:08.759 --> 00:28:12.500 the cranial nerves here right you have um the 00:28:12.500 --> 00:28:16.369 superior colliculus which is receiving Eyes, 00:28:16.509 --> 00:28:19.769 eye movements. You hear a sound over here and 00:28:19.769 --> 00:28:21.910 you're just, you know, it's just reflexive. This 00:28:21.910 --> 00:28:25.549 is a very powerful area. And like barn owls, 00:28:25.690 --> 00:28:28.470 it's called optic tectum. Great research on that 00:28:28.470 --> 00:28:33.410 with Eric Knudsen. Knudsen from Stanford. Go 00:28:33.410 --> 00:28:36.650 see his stuff, man. He has great papers. But 00:28:36.650 --> 00:28:39.930 this also incorporates sound, right? Because 00:28:39.930 --> 00:28:42.630 if you hear a sound to your left and you automatically 00:28:42.630 --> 00:28:45.730 look, you can pick up that target pretty accurately. 00:28:48.589 --> 00:28:55.710 That's so reflexive. And then overall, this little 00:28:55.710 --> 00:29:00.089 area here is orienting attention. But what kind 00:29:00.089 --> 00:29:04.069 of attention? To the outside world. All of this 00:29:04.069 --> 00:29:09.609 stuff is receiving information fast from the 00:29:09.609 --> 00:29:15.930 outside world and then kind of recruiting distal 00:29:15.930 --> 00:29:19.849 areas, right? Substantial Niagara with the basal 00:29:19.849 --> 00:29:27.390 ganglia, eye movements, hearing. PAG is big with 00:29:27.390 --> 00:29:30.809 pain perception and just kind of, you've probably 00:29:30.809 --> 00:29:33.890 heard, I know you've heard of fight. flight or 00:29:33.890 --> 00:29:38.910 freeze. When we freeze, the PAG receives information 00:29:38.910 --> 00:29:43.529 from areas like the hypothalamus and probably 00:29:43.529 --> 00:29:48.890 the habinula and the amygdala. The para -aqueductal 00:29:48.890 --> 00:29:51.670 gray. When we freeze, remember there's a lot 00:29:51.670 --> 00:29:54.410 of ganglionic fibers running down the spine from 00:29:54.410 --> 00:29:58.230 this area. This thing is shut off. This thing 00:29:58.230 --> 00:30:01.049 shuts the spine off and it just shuts your motor 00:30:01.049 --> 00:30:04.589 movements off. It's so powerful. This area right 00:30:04.589 --> 00:30:09.789 here is so powerful. But this right here, these 00:30:09.789 --> 00:30:13.789 three things is the Autistic Phenotype. You name 00:30:13.789 --> 00:30:19.329 me, you go find me one Autistic Phenotype that 00:30:19.329 --> 00:30:21.769 does not have problems with the Central Nervous 00:30:21.769 --> 00:30:24.109 System, the Peripheral Nervous System, and the 00:30:24.109 --> 00:30:27.730 Enteric Nervous System. You can't. You can't 00:30:27.730 --> 00:30:31.990 find it. This is also involved because I mentioned 00:30:31.990 --> 00:30:36.890 the reticular formation with sleep, the mesencephalon, 00:30:36.970 --> 00:30:42.569 and even this brainstem. So here we go. The reticular 00:30:42.569 --> 00:30:46.069 formation is just a collection of areas here 00:30:46.069 --> 00:30:49.809 within the brainstem, just like different areas. 00:30:50.769 --> 00:30:55.710 And it has ascending and descending fibers. The 00:30:55.710 --> 00:30:59.269 reticular formation Big with this of course it 00:30:59.269 --> 00:31:03.049 is so let's talk about that Picture of the Parkinson's 00:31:03.049 --> 00:31:05.630 because you can look this up. This is this isn't 00:31:05.630 --> 00:31:11.250 hard to find Okay, so I'll do brown because it's 00:31:11.250 --> 00:31:15.390 supposed to be like Tissue, okay, so let's draw 00:31:15.390 --> 00:31:18.630 this out real fast just real loosely. It doesn't 00:31:18.630 --> 00:31:23.529 matter How good it is or accurate? Okay, so we 00:31:23.529 --> 00:31:27.559 have this cerebral uncle thing then I want to 00:31:27.559 --> 00:31:30.119 draw another one okay and then the substantial 00:31:30.119 --> 00:31:35.779 nigra here right here this is Parkinson's it's 00:31:35.779 --> 00:31:39.359 black remember because it has neuromelanin in 00:31:39.359 --> 00:31:43.019 it it's loaded with neuromelanin these areas 00:31:43.019 --> 00:31:46.359 right here because it's full of water melanin 00:31:46.359 --> 00:31:49.920 and water is our energy source this is biological 00:31:49.920 --> 00:31:52.519 energy the blood -brain barrier here is very 00:31:52.519 --> 00:31:54.700 weak because there's so much water. There's so 00:31:54.700 --> 00:31:58.119 much electrical power coming through here. So 00:31:58.119 --> 00:32:03.400 with healthy people, the substantia nigra is 00:32:03.400 --> 00:32:08.099 dark because of that neuromelanin. With Parkinson's, 00:32:08.440 --> 00:32:11.000 you can barely see tissue. You can barely see 00:32:11.000 --> 00:32:13.680 it with Parkinson's because their neuromelanin 00:32:13.680 --> 00:32:20.299 is gone. And this and this and this right here. 00:32:20.519 --> 00:32:22.579 It's controlling movements. You think about the 00:32:22.579 --> 00:32:26.200 autistic phenotype and stereotyping. Stemming. 00:32:26.319 --> 00:32:28.160 We'll do some more stuff on the basal ganglia. 00:32:28.359 --> 00:32:33.000 This little epoch of time is so underrated. I 00:32:33.000 --> 00:32:34.940 feel like so much of what we talk about is just 00:32:34.940 --> 00:32:37.059 so underrated. Is that because autism research 00:32:37.059 --> 00:32:40.220 just finds things and nothing is followed up? 00:32:40.519 --> 00:32:42.960 But, mesencephalon. This is why I'm so fascinated 00:32:42.960 --> 00:32:43.960 with the mesencephalon.